2013 Fiscal Year Final Research Report
Development of a bioassay system to screen anti-aging chemicals and characterization of candidate molecules
| Project/Area Number |
24659181
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Waseda University |
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Principal Investigator |
CHIBA Takuya 早稲田大学, 人間科学学術院, 教授 (40336152)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 老化 / トランスジェニックマウス / 機能性食品 / ガン / 臓器連関 / メタボリックシンドローム / カロリー制限 / 転写因子 |
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| Research Abstract |
In this study, we tried to identify the intracellular signaling pathways and develop a system to screen anti-aging chemicals both in vitro and in vivo. We found that one of the synthesized sequences of identified motifs bound to hepatocyte nuclear factor-4 (HNF-4). When the reporter construct, containing an element upstream of a secreted alkaline phosphatase (SEAP) gene, was co-transfected with HNF-4 and its regulator peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1), activity of SEAP was increased dose-dependently in comparison to untransfected controls. Moreover, transgenic mice established using this construct showed increased SEAP activity both calorie restriction (CR) and candidate chemical-fed mice in comparison to ad libitum fed mice. Interestingly, oxidative stress resistance was correlated with SEAP activity of these transgenic mice. These data suggest that our bioassay would be useful to screen for CR mimetic photochemical both in vitro and in vivo.
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